17β-Estradiol and progesterone decrease MDP induced NOD2 expression in bovine mammary epithelial cells

Abstract During the periparturient period, many neuroendocrine changes develop in cows. Periparturient hormone fluxes may adversely affect mammary gland immunity and mastitis susceptibility. 17β-Estradiol (E 2 ) and progesterone (P 4 ) have been reported to function on immune regulation, and their concentration fluctuates dramatically during the perinatal period. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) mediate numerous aspects of innate immunity in humans and experimental animals. This study aimed to explore the effects of E 2 and P 4 on NOD2 expression in bovine mammary epithelial cells (BMECs). BMECs were isolated and purified from bovine mammary tissue and treated with E 2 /P 4 and muramyl dipeptide (MDP). After these treatments, the mRNA levels of NOD2, receptor-interacting protein kinase ( RIP ) 2, interleukin ( IL ) 1β, IL-6 , IL-8 and tumor necrosis factor ( TNF ) α were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) respectively, and the protein levels of NOD2 were analyzed by western blotting. The results showed that E 2 and P 4 decreased MDP-induced transcriptional expression of NOD2 and the downstream molecules. Moreover, E 2 reduced MDP-induced NOD2 protein expression levels. Our study suggests that down-regulation of NOD2 by E 2 and P 4 may be one of the reasons for mastitis susceptibility in periparturient dairy cows.